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Tuesday, February 28, 2023

Sunshine Bioipharma Licenses PLpro-Based Covid-19 Treatment

 Sunshine Biopharma Inc. (NASDAQ: “SBFM”), a pharmaceutical company offering and researching life-saving medicines in a variety of therapeutic areas including oncology and antivirals today announced the signing of an exclusive worldwide license agreement (the “License Agreement”) with the University of Arizona. The License Agreement grants Sunshine Biopharma exclusive worldwide rights for all of the University of Arizona and University of Illinois Chicago technology pertaining to PLpro protease inhibitors of SARS-CoV-2, the coronavirus that causes COVID-19. Sunshine Biopharma has been working on this project in collaboration with the University of Arizona since February 2022. The collaboration granted Sunshine Biopharma an exclusive option to obtain a license for the related technology.

Specifically, the licensed technology covers small molecules which have been shown to be efficient inhibitors of PLpro, the second coronavirus protease responsible for suppression of the human immune system thereby making the SARS-CoV-2 virus capable of causing more severe illness. Paxlovid®, an inhibitor for the first protease of SARS-CoV-2 (Mpro) has recently received emergency use authorization from the FDA. Sunshine Biopharma believes that an inhibitor for the second protease will provide another target to combat the virus and help mitigate the occurrence of possible resistance events.

https://finance.yahoo.com/news/sunshine-biopharma-signs-exclusive-worldwide-123000850.html

Cardio Diagnostics Launches Blood Test for Early Detection of Coronary Heart Disease

 PrecisionCHD is the First Integrated Epigenetic-Genetic-Based Blood Test for the Early Detection of Coronary Heart Disease

Cardio Diagnostics Holdings Inc (Nasdaq: CDIO), an artificial intelligence-powered precision cardiovascular medicine company, today announced the launch of PrecisionCHD, an integrated epigenetic-genetic blood test for the early detection of coronary heart disease.

PrecisionCHD is the second clinical test built using Cardio Diagnostics’ proprietary AI-driven Integrated Epigenetic-Genetic Engine. The company’s initial product, Epi+Gen CHD, a three-year coronary heart disease risk assessment test, also leveraged the Engine and was launched in 2021. The two tests address the most common form of cardiovascular disease – coronary heart disease – across the entire spectrum, from assessing risk for prevention to early detection. Over the next two years, Cardio Diagnostics expects to continue to leverage its Engine to develop a series of integrated epigenetic-genetic clinical tests for other cardiovascular diseases and associated conditions.

Cardiovascular disease (CVD) continues to be the leading cause of death in the United States, with coronary heart disease (CHD) being the most common type of CVD and the primary cause of heart attacks. According to the American Heart Association, nearly 400,000 deaths in 2020 are attributable to CHD, and over 800,000 Americans have a heart attack yearly. Cardio Diagnostics’ new patent-pending test, PrecisionCHD, aids in the early detection of coronary heart disease to better enable the management of this condition to prevent a symptomatic event such as a heart attack.

Using epigenetic (DNA methylation) and genetic (single nucleotide polymorphism) biomarkers along with a proprietary machine-learning model developed by analyzing billions of genomic and epigenomic data points, PrecisionCHD detects coronary heart disease with better than 75% sensitivity in both men and women. A key defining characteristic of PrecisionCHD is its accompanying provider-only Actionable Clinical Intelligence platform, which maps a patient’s unique biomarker profile onto modifiable risk factors such as diabetes, hypertension, hypercholesterolemia, and smoking, known to be critical drivers of coronary heart disease.

America’s Racialized Medical Schools

 Earlier this month, the White House announced a five-year plan for redressing racial inequality. It is essentially the Biden administration’s version of a diversity, equity, and inclusion (DEI) plan, like those issued by nearly every major university, only at a vastly larger scale. The policy aims to “advance an ambitious, whole-of-government approach to racial equity and support for underserved communities” by embedding equity goals in every aspect of the government.

From the highest offices of the state down to the smallest local bureaucracies, DEI now pervades almost all levels of American society. And while it was once thought that the fringe racial theories that animate the DEI agenda could be confined to small liberal arts campuses, it is clear that is no longer the case.

Increasingly, medical schools and schools of public health are enthusiastically embracing the values of DEI and instituting far-reaching policies to demonstrate their commitments to the cause. To many in the universities and perhaps in the country at large, these values sound benign—merely an invitation to treat everyone fairly. In practice, however, DEI policies often promote a narrow set of ideological views that elevate race and gender to matters of supreme importance.

That ideology is exemplified by a research methodology called “public health critical race praxis” (PHCRP)—designed, as the name suggests, to apply critical race theory to the field of public health—which asserts that “the ubiquity of racism, not its absence, characterizes society’s normal state.” In practice, PHCRP involves embracing sweeping claims about the primacy of racialization, guided by statements like “socially constructed racial categories are the bases for ordering society.”

These race-first imperatives have now come to influence the research priorities of major institutions. Perhaps no better case study exists than that of the University of California, San Francisco (UCSF), an institution devoted exclusively to the medical sciences, and one of the top recipients of federal grants from the National Institutes of Health. Last May, UCSF took the unprecedented step of creating a separate Task Force on Equity and Anti-Racism in Research, which proceeded to make dozens of recommendations.

That task force builds on layers of prior DEI bureaucratic expansion, spanning nearly a decade. This programming includes the “UCSF Anti-Racism Initiative,” started after the summer of 2020, which established dozens of new institutional policies throughout the university, such as “evaluating contributions to diversity statements in faculty advancement portfolios.” The School of Medicine, meanwhile, has published its own Timeline of DEI and Anti-Racism Efforts, which documents such steps as adding a “social justice pillar” to the school’s curriculum and creating an anti-racist curriculum advisory committee.

The policies often promote an idiosyncratic and controversial understanding of concepts like diversity and racism. Through its Difference Matters initiative, the medical school created a document titled “Anti-Racism and Race Literacy: A Primer and Toolkit for Medical Educators”—which is filled with eyebrow-raising assertions. Racism, the guide asserts, “refers to the prioritization of the people who are considered white and the devaluation, exploitation, and exclusion of people racialized as non-white.” Anti-racism, meanwhile, involves directly shifting power from those who are white to those who are Black. “Anti-racism examines and disrupts the power imbalances between racialized and non-racialized people (white people), to shift power away from those who have been historically over-advantaged and towards people of color, especially Black people.” Of course, when applied to the allocation of lifesaving medical care, these ideals can carry weighty consequences. During the height of the COVID pandemic, New York, Minnesota, and Utah issued guidance for allocating monoclonal antibodies that heavily prioritized racial and ethnic minorities.\

While this hyper-racialized approach has long been the norm in humanities departments, it now appears to have fully crossed over into the hard sciences as well, with medical schools leading the charge. Med schools across the country have aggressively embraced DEI programming, often instituting policies that promote a narrow vision of social justice. In 2021, the University of Michigan Medical School created its Anti-Racism Oversight Committee Action Plan, making a set of new policy recommendations that had won the endorsement of the medical school’s leadership. That action plan called for a new curriculum to help inculcate a “demonstrated increase in understandings of DEI, antiracism, and intersectionality concepts in medical students and residents.” For medical residents, the plan stipulated that the curriculum should be based on Ibram X. Kendi’s book Stamped from the Beginning.

Some of these initiatives create obvious issues of academic freedom. In 2020, the UNC School of Medicine created a “Task Force for Integrating Social Justice Into the Curriculum,” issuing a report with dozens of recommendations. One called for faculty to adhere to “core concepts of anti-racism,” listing several of these required “concepts,” including “race is not a set biological category” and “specific organs and cells do not belong to specific genders.” The task force also called for students to “be trained in core advocacy skills”—even listing a number of political causes that it deemed important for students to embrace. These causes, which the report labeled “health realms,” included “restoring U.S. leadership to reverse climate change,” and “achieving radical reform of the US criminal justice system.” The school initially listed every recommendation as “On Time” on an online implementation tracker, though it eventually walked back some of the more controversial requirements.

All of this comes under the broad umbrella of “diversity, equity, and inclusion,” illustrating how the term is both far more radical and more deeply entrenched than its defenders often claim.\\

Shorn of any context, the principles of diversity and inclusion strike many people as unobjectionable, and even laudable. But in practice they are used as a shorthand for a set of divisive ideological dogmas and bureaucratic power grabs. Under the banner of DEI, medical institutions that are supposed to focus on protecting human life are being sacrificed on the altar of the racialist ideology.

Because of the ideological project associated with DEI initiatives, critics often highlight their effect on curriculum and teaching. But the more potent effect, in the long run, could end up being on scientific research and scholarship.

For the UCSF Task Force on Equity and Anti-Racism in Research, the stated goal is to transform the university’s research enterprise. “To truly rectify the entrenched, structural harms from racism in research,” the task force report notes, “we must start from its foundations in the way that we privilege knowledge, methods, and people. The overarching changes required to mitigate racism in research is a philosophical shift in the mindset of those in power and those who produce research.”

Although the policies listed in the report are only recommendations, some have already been implemented, and many are likely to be in the future. The report’s first recommendation, for example, calls for a new vice chancellor for DEI in research. In September, UCSF announced the role was given to Tung Nguyen, co-chair of the task force. The report—referred to by Nguyen as a “labor of love and trauma”—states that the recommended policies will show that “anti-racism” is “centered in all aspects of the way we work and function as a research enterprise.” That includes emphasizing diversity statements even more strongly in the promotion and tenure process, and evaluating university leadership along such lines as their “record of hiring women and members of historically excluded populations.” Not necessarily the qualities that people suffering from serious illnesses would look for in their medical care providers.

The task force calls for inserting similar DEI requirements into its research enterprise and adding “scoring criteria on equity and anti-racism” to UCSF’s internal grant programs. It recommends expanding UCSF’s existing anti-racism research grant program—something Nguyen has emphasized since taking his new role. The report itself links to UCSF’s “Pilot for Anti-Racism Research” program, which funds small research projects within the university. That program provides perhaps the clearest articulation of what UCSF means by “anti-racism research.” It borrows the language of UCSF’s “Anti-Racism and Race Literacy” guide, noting: “Anti-racism examines and disrupts the power imbalances between racialized and non-racialized people, to shift power away from those who have been historically over-advantaged and towards people of color.” It later adds, “Anti-racism research uses approaches such as the Public Health Critical Race Praxis for applying Critical Race Theory to empirical research.”

In other words, under the new ideological regime that has taken power both inside the federal bureaucracy and in institutions like UCSF, even medical research has become yet another front in a larger ideological battle. Tomorrow’s doctors and medical experts are being selected and trained on the basis of their willingness to “disrupt power imbalances between racialized and non-racialized people.”

Much of the report raises obvious concerns. Some, for instance, might reject the task force’s assertion that racism pervades all areas of the university—especially in such a progressive bastion as UC San Francisco. It is telling that the university seems to actively encourage this assumption in research, but also unsurprising—after all, the “ordinariness of racism” is one of the tenets of public health critical race praxis, which is now being pushed by Nguyen under the guise of anti-racism research.

More broadly, many of these measures could pose a threat to academic freedom. Organizations such as the Academic Freedom Alliance and the Foundation for Individual Rights and Expression have argued against mandatory diversity statements. After all, given that DEI is often associated with a narrow set of social and political views, it’s not hard to see how evaluating a professor’s commitment to DEI invites viewpoint discrimination. An “anti-racism” advisory board that reviews grants would only extend that policy further.

By the time it published the report, the UCSF task force was aware of all of these issues. Each had been brought up by UCSF employees during the comment period. The comments were published in the report’s appendixes, which make up perhaps the most telling part of the whole publication.

One commenter repeated the same line in every answer: “I fundamentally do not feel or have ever felt that UCSF is a racist place. These are grossly misdirected funds and efforts.” Several cautioned against embracing discriminatory policies in the name of anti-racism. “All of the above sounds to me like trying to fight racism with more racism,” one noted. Still others urge the task force not to distract from UCSF’s focus on scientific research. As one commenter put it, “UCSF is a medical and life science campus. Its strength lies in its objective data-driven experimental approach. Qualitative and sociological research has no place at UCSF and no place in scientific medical research and will undermine UCSF’s reputation.”

Yet rather than addressing the concerns of the school’s employees, the report attacks them while presenting its authors as the real victims.

It is important to note that while many of the comments received were constructive and helpful, task force members were traumatized by a striking number of comments that denied the existence of inequities and racism, and others that minimized the burden that racism has imposed, particularly on Black Americans at UCSF.

The forward to the report quotes one of the task force co-chairs, Sun Yu Cotter, who adds:

It is extremely important to acknowledge the magnitude of the emotional labor and trauma that many of the Task Force members endured in doing this work, particularly during the public comment period. Not only are many of the Task Force members, especially our Black colleagues, encountering and navigating racism on a daily basis at work and outside of work, we are also volunteering our very limited time to dive into grueling work (the minority tax is real!). Then to be gaslit by some members of our very own UCSF community was very painful.

Take note. This is the future of American medicine.

John Sailer is a fellow at the National Association of Scholars.

https://www.tabletmag.com/sections/news/articles/americas-racialized-medical-schools

Arrowhead: Positive interim data from RNA interference (RNAi) therapeutic study

 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced interim results from Part 1 of AROC3-1001, an ongoing Phase 1/2 clinical study of ARO-C3, the company’s investigational RNA interference (RNAi) therapeutic designed to reduce production of complement component 3 (C3) as a potential therapy for various complement mediated diseases. The company plans to present additional results at an upcoming complement-focused medical meeting. Dosing in Part 2 of the Phase 1/2 study is expected to begin in the first half of 2023.

In Part 1 of AROC3-1001, ARO-C3 interim results included:

  • A dose-dependent reduction in serum C3, with 88% mean reduction at highest dose tested

  • A dose-dependent reduction in AH50, a marker of alternative complement pathway hemolytic activity, with 91% mean reduction at highest dose tested

  • Duration of pharmacologic effect supportive of quarterly or less frequent subcutaneous dose administration

  • Safety and tolerability

    • Overall, no clinically significant laboratory findings or patterns of adverse changes in any clinical laboratory parameters

    • No dose limiting toxicity, serious or severe adverse events, or study discontinuation due to adverse events

    • Most common adverse events include headache, COVID-19, generally mild injection site reactions, and seasonal allergy

"ARO-C3 has achieved encouraging results in Part 1 of this Phase 1/2 clinical study, including a mean reduction of 88% in C3 and 91% in AH50 at the highest dose tested. These data in healthy volunteers provide us with further confidence as we begin Part 2 of the study, which includes patients with various complement mediated diseases," said James Hamilton, M.D., MBA, chief of discovery and translational medicine at Arrowhead. "Substantial unmet medical need remains in the treatment of multiple complement mediated diseases, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and additional renal and hematologic indications, despite the availability of approved complement C5 inhibitors that have significantly improved treatment. In addition, we believe C3 inhibition has interesting potential, as it is upstream of C5 in the complement cascade."

Jaguar Gets Orphan Tag for 2nd Rare Disease Indication

  Jaguar Health (NASDAQ:JAGX) ("Jaguar" or the "Company") today announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to crofelemer for the indication of microvillus inclusion disease (MVID), a rare congenital diarrheal disorder (CDD) condition, following review of the ODD application the Company submitted to the FDA.

"This is another very welcome development for our oral botanical drug, crofelemer, a new molecular entity that now holds four orphan designations, as crofelemer previously received ODD for MVID from the European Medicines Agency (EMA) and for short bowel syndrome (SBS) from both the FDA and the EMA," said Lisa Conte, Jaguar's president and CEO.

https://www.biospace.com/article/releases/fda-grants-orphan-drug-designation-to-jaguar-health-for-crofelemer-for-microvillus-inclusion-disease-mvid-a-second-rare-disease-indication-in-the-us/

Kyverna and Cabaletta are Repurposing CAR-T for Autoimmune Diseases

 Researchers at Kyverna Therapeutics and Cabaletta Bio hope to repurpose CAR-T cell therapy for patients with autoimmune diseases. 

CAR-T cell therapy, or chimeric antigen receptor T cell therapy, is best known for its application in oncology, where the results have been life-changing for patients. Approved and experimental CAR-T therapies have resulted in reductions in death and progression of the disease and have jumpstarted remission in several malignancies.

This approach is applied in treating autoimmune diseases, chronic conditions in which the body’s immune system attacks healthy cells.

CAR-T cell therapy for autoimmune diseases made headlines in September 2022 when five patients with systemic lupus erythematosus (SLE) were confirmed to be in remission for an average of eight months after treatment. There were no signs of relapse in the first patient to receive the therapy after 17 months of follow-up.

The study, led by Friedrich Alexander University Erlangen-Nuremberg researchers, was published in Nature Medicine.

Why CAR-T? 

In autoimmune disease, the body produces autoreactive B cells, immune cells that produce antibodies against healthy cells and autoantigens, inviting T cells to produce an autoimmune response.

These autoreactive B cells are responsible for the symptoms and inflammation in patients with autoimmune diseases as they attack cells that perform essential bodily functions.

“Autoimmune disease is caused when a person’s immune system comes to see some part of the body as foreign; this is called ‘breaking tolerance,’” Gwen Binder, Ph.D., president of science and technology, Cabaletta Bio, told BioSpace

She said this effect usually results from genetics, environment, general health status and infection history.  

Once tolerance breaks, the proliferation of autoimmune reactions in the body begins.

CAR-T therapy can be beneficial as the therapy can specifically attack and deplete these autoreactive B cells within the body.

“Complete elimination of these autoreactive B cells in the blood and tissue reservoirs, something CAR-T cells can do but B cell-depleting antibodies cannot, could remove the central initiator and driver of autoimmunity,” Binder said.

CAR-T could offer a potential long-term solution to these chronic conditions.

Therapies Move Forward

Cabaletta is developing CABA-201, a fully human CD19 CAR containing a 4-1BB co-stimulatory domain.

Binder said the design of CABA-201 is similar to the one used in the German study where patients achieved remission. 

Cabaletta’s fully human CD19 binder has demonstrated a favorable tolerability profile in approximately 20 patients. The 4-1BB co-stimulatory domain is associated with less frequent serious adverse events like cytokine release syndrome, Binder said.

CABA-201 is in preclinical studies for several undisclosed indications. It could target various autoimmune diseases, including SLE, rheumatoid arthritis and systemic sclerosis.

In Emeryville, California, Kyverna is developing KYV-101 for lupus nephritis. The FDA cleared the Investigational New Drug application for the CAR-T therapy in November 2022.  

Peter Maag, Ph.D., CEO, told BioSpace that while other treatments for lupus show a 20% improvement over baseline, with multiple CAR-T therapy studies, he's seen a 100% complete response.

KYV-101 maximizes B cell depletion while minimizing cytokine release to avoid adverse events during CAR-T treatment. The release of cytokines can also be detrimental in an autoimmune environment.

In preclinical studies, CD19-targeted CAR-T cell therapies have demonstrated complete B cell depletion in circulation and tissues.

Early Days 

It’s too early to know how effective CAR-T cell therapies will be for patients with autoimmune diseases.

If a one-time administration of CD19-CAR-T can deplete all of the B cells in the body, Binder said it’s possible to reset the immune system and conceptually cause “long-lasting disease remission off therapy.” 

More robust datasets are needed; however, CAR-T may not work in all cases. 

Maag said that without long-term data, it’s impossible to tell how long the remission might last. But he reiterated Binder’s contention, saying CAR-T is “a complete resetting of the immune system for a substantial amount of time,” something that has never occurred in the autoimmune space. 

As cell manufacturing costs decrease and the potential to scale increases, Maag said now is the perfect time to design CAR-T therapies against autoimmune diseases. 

But the time is also ripe for those suffering from autoimmune diseases to experience innovative treatments that address their concerns.

“Patients can benefit from participating in a clinical trial,” he said.

https://www.biospace.com/article/repurposing-car-t-for-autoimmune-diseases-kyverna-and-cabaletta-bio/

CIA Played Key Role In Nelson Mandela's Arrest & Imprisonment: Time

 A newly unearthed interview along with declassified documents point to CIA involvement in the 1962 arrest of anti-apartheid leader Nelson Mandela by the US-friendly apartheid government. At that time, the height of the Cold War, Mandela was seen as part of the Communist opposition.

Time magazine in a new bombshell report asks the question, "Did the CIA Betray Nelson Mandela?" and comes to the conclusion that there was pivotal involvement of America's most powerful spy agency. 

The details are coming to light based on the work of Richard Stengel, collaborator on Mandela's autobiography, "Long Walk to Freedom". Stengel revisited an unpublished 1993 audio interview he had captured with Mandela, wherein the famous anti-apartheid activist and eventual South African president told him he had learned that an American consul with CIA connections had briefed South African authorities on Mandela's travel habits.

This would help lead to Mandela's arrest and imprisonment for 27 years as head of the outlawed African National Congress (ANC). Additionally now declassified CIA documents had labeled Mandela "probably communist" and confirmed that the agency had been closely tracking him anytime he went out of South Africa.

This was during the presidency of John F. Kennedy. According to Axios, "Taken together, Stengel says, the details add significantly to the evidence that the CIA was tracking Mandela and helped South African authorities arrest him as he was traveling from Durban to Johannesburg in 1962."

And according to further details revealed in the Time report: 

  • A Johannesburg Star story in 1986 cited a "retired senior police officer" saying South African police had been tipped off to Mandela's whereabouts by a U.S. diplomat in Durban who was "the CIA operative for that region."

  • Four years later, the Atlanta Journal-Constitution reported that a "retired [American] intelligence official" identified a "senior CIA operative" as giving South Africa every detail about Mandela's whereabouts.

The details are also consistent with how the US government classified Mandela and his African National Congress throughout the 1980s and 1990s. 

Despite US officials and media now praising his civil rights legacy as a unifier, the reality is successive US administrations considered him a "terrorist" and actively opposed him and his racial equality movement. 

A 2013 NBC report pointed to the historical irony and hypocrisy of US officials as follows: "Until five years ago, however, the U.S. officially considered Mandela a terrorist. During the Cold War, both the State and Defense departments dubbed Mandela’s political party, the African National Congress, a terrorist group, and Mandela’s name remained on the U.S. terrorism watch list till 2008." And more from the report: 

But in 1986, Reagan condemned Mandela’s group, the ANC, which was leading the black struggle against the apartheid regime, saying it engaged in "calculated terror ... the mining of roads, the bombings of public places, designed to bring about further repression."

There's long been speculation that the CIA played a key role in Mandela's capture and imprisonment, but more and more details are still being proven, also as three-decade old intelligence files come up for periodic declassifications. He was South Africa's first black head of state starting in 1994, and died in 2013 at the age of 95.

https://www.zerohedge.com/geopolitical/new-evidence-cia-played-key-role-nelson-mandelas-arrest-imprisonment